Inhibitory role of bone marrow mesenchymal stem cells‐derived exosome in non‐small‐cell lung cancer: microRNA‐30b‐5p, EZH2 and PI3K/AKT pathway

Abstract

AbstractExosomal microRNA (miRNA) exerts potential roles in non‐small‐cell lung cancer (NSCLC). The current study elucidated the role of miR‐30b‐5p shuttled by bone marrow mesenchymal stem cells (BMSCs)‐derived exosomes in treating NSCLC. Bioinformatics analysis was performed with NSCLC‐related miRNA microarray GSE169587 and mRNA data GSE74706 obtained for collection of the differentially expressed miRNAs and mRNAs. The relationship between miR‐30b‐5p and EZH2 was predicted and confirmed. Exosomes were isolated from BMSCs and identified. BMSCs‐derived exosomes overexpressing miR‐30b‐5p were used to establish subcutaneous tumorigenesis models to study the effects of miR‐30b‐5p, EZH2 and PI3K/AKT signalling pathway on tumour growth. A total of 86 BMSC‐exo‐miRNAs were differentially expressed in NSCLC. Bioinfomatics analysis found that BMSC‐exo‐miR‐30b‐5p could regulate NSCLC progression by targeting EZH2, which was verified by in vitro cell experiments. Besides, the target genes of miR‐30b‐5p were enriched in PI3K/AKT signalling pathway. Animal experiments validated that BMSC‐exo‐miR‐30b‐5p promoted NSCLC cell apoptosis and prevented tumorigenesis in nude mice via EZH2/PI3K/AKT axis. Collectively, the inhibitory role of BMSC‐derived exosomes‐loaded miR‐30b‐5p in NSCLC was achieved through blocking the EZH2/PI3K/AKT axis.